AR083492A1 - AMINIC DERIVATIVES FOR THE TREATMENT OF SKIN PROLIFERATIVE DISORDERS - Google Patents

AMINIC DERIVATIVES FOR THE TREATMENT OF SKIN PROLIFERATIVE DISORDERS

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Publication number
AR083492A1
AR083492A1 ARP110103881A ARP110103881A AR083492A1 AR 083492 A1 AR083492 A1 AR 083492A1 AR P110103881 A ARP110103881 A AR P110103881A AR P110103881 A ARP110103881 A AR P110103881A AR 083492 A1 AR083492 A1 AR 083492A1
Authority
AR
Argentina
Prior art keywords
group
groups
halogen atoms
optionally substituted
alkyl
Prior art date
Application number
ARP110103881A
Other languages
Spanish (es)
Inventor
Marina Nuria Godessart
Pelaez Cristina Balague
Original Assignee
Almirall Sa
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Almirall Sa filed Critical Almirall Sa
Publication of AR083492A1 publication Critical patent/AR083492A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents

Abstract

Se describen composiciones que comprenden derivados amínicos específicos para su uso en el tratamiento de enfermedades o trastornos proliferativos de la piel y el uso de derivados amínicos específicos en dicho tratamiento.Reivindicación 1: Un derivado amínico de fórmula (1): A-NH-B (1) o una sal farmacéuticamente aceptable o N-óxido o solvato o derivado deuterado del mismo, para uso en el tratamiento de una enfermedad o trastorno proliferativo de la piel, en donde: A representa un grupo de fórmula (A1) ó (A2), en donde el símbolo asterisco indica el enlace que está unido al resto -NH-B; y en donde: en el grupo de fórmula (A1): R1 representa un grupo seleccionado de átomos de hidrógeno, halógeno, grupos alquilo C1-4 que pueden estar opcionalmente sustituidos con 1, 2 ó 3 sustituyentes seleccionados de átomos de halógeno y grupos hidroxi, y grupos cicloalquilo C3-8 que pueden estar opcionalmente sustituidos con 1, 2 ó 3 sustituyentes seleccionados de átomos de halógeno y grupos hidroxi; uno de los grupos G3 y G4 es un átomo de nitrógeno y el otro es un grupo CH; M es un átomo de hidrógeno o un catión farmacéuticamente aceptable; en el grupo de fórmula (A2): R1’ se selecciona del grupo que consiste en átomos de hidrógeno, átomos de halógeno, alquilo C1-4, cicloalquilo C3-4, -CF3 y -OCF3; R2’ se selecciona del grupo que consiste en átomos de hidrógeno, átomos de halógeno y grupo alquilo C1-4; R3’ se selecciona del grupo que consiste en los grupos -COOR5’, -CONHR5’, tetrazolilo, -SO2NHR5’ y -CONHSO2R5’, en donde R5’ se selecciona del grupo que consiste en un átomo de hidrógeno y grupos alquilo C1-4 lineales o ramificados; B representa un grupo de fórmula (B1) ó (B2), en donde el símbolo asterisco indica el enlace que está unido al resto A-NH-; y en donde: en el grupo de fórmula (B1): uno de los grupos G1 representa un átomo de nitrógeno o un grupo CRc y el otro representa un grupo CRc; G2 representa un átomo de nitrógeno o un grupo CRd; R2 representa un grupo seleccionado de átomos de hidrógeno, átomos de halógeno, grupos hidroxilo, grupos alquilo C1-4 que pueden estar opcionalmente sustituidos con 1, 2 ó 3 sustituyentes seleccionados de átomos de halógeno y grupos hidroxi, grupos alcoxi C1-4 que pueden estar opcionalmente sustituidos con 1, 2 ó 3 sustituyentes seleccionados de átomos de halógeno y grupos hidroxi, y grupos cicloalquilo C3-8 que pueden estar opcionalmente sustituidos con 1, 2 ó 3 sustituyentes seleccionados de átomos de halógeno y grupos hidroxi; Ra, Rb, Rc independientemente representan grupos seleccionados de átomos de hidrógeno, átomos de halógeno, grupos alquilo C1-4 que pueden estar opcionalmente sustituidos con 1, 2 ó 3 sustituyentes seleccionados de átomos de halógeno y grupos hidroxi, y grupos alcoxi C1-4 que pueden estar opcionalmente sustituidos con 1, 2 ó 3 sustituyentes seleccionados de átomos de halógeno y grupos hidroxi; Rd representa un grupo seleccionado de átomos de hidrógeno, átomos de halógeno, grupos hidroxilo, grupos alquilo C1-4 que pueden estar opcionalmente sustituidos con 1, 2 ó 3 sustituyentes seleccionados de átomos de halógeno y grupos hidroxi, y grupos alcoxi C1-4 que pueden estar opcionalmente sustituidos con 1, 2 ó 3 sustituyentes seleccionados de átomos de halógeno y grupos hidroxi, y grupos cicloalcoxi C3-8 que pueden estar opcionalmente sustituidos con 1, 2 ó 3 sustituyentes seleccionados de átomos de halógeno y grupos hidroxi; con la condición de que, cuando al menos uno de los grupos Ra y Rb representa un átomo de hidrógeno y G2 es un grupo CRd, entonces Rd representa un grupo seleccionado de grupos alcoxi C1-4 que pueden estar opcionalmente sustituidos con 1, 2 ó 3 sustituyentes seleccionados de átomos de halógeno y grupos hidroxi, grupos cicloalcoxi C3-8 que pueden estar opcionalmente sustituidos con 1, 2 ó 3 sustituyentes seleccionados de átomos de halógeno y grupos hidroxi; en el grupo de fórmula (B2): R4’ se selecciona del grupo que consiste en un átomo de hidrógeno, y un grupo alquilo C1-4; R9’ se selecciona del grupo que consiste en un átomo de hidrógeno y un grupo fenilo; G1’ representa un grupo seleccionado de N y CR6’ en donde R6’ se selecciona del grupo que consiste en átomos de hidrógeno, átomos de halógeno, alquilo C1-4, cicloalquilo C3-4, alcoxi C1-4, -CF3, -OCF3, heteroarilo monocíclico C5-7 que contiene N, grupos heterociclilo C3-7 monocíclicos que contienen N y un grupo arilo C6-10 que está opcionalmente sustituido con uno o más sustituyentes seleccionados de átomo de halógeno y un grupo alquilo C1-4; G2’ representa un grupo seleccionado de: i) un átomo de hidrógeno, un grupo hidroxi, un átomo de halógeno, un grupo cicloalquilo C3-4, un grupo alcoxi C1-4 y -NRa’Rb’, en donde Ra’ representa un grupo alquilo C1-4 y Rb’ se selecciona de un grupo que consiste en grupo alquilo C1-4 y grupo alcoxi C1-4-alquilo C1-4; o Ra’ y Rb’ junto con el átomo de nitrógeno al que están unidos forman un anillo heterocíclico saturado de 6 a 8 miembros que contiene opcionalmente un átomo de oxígeno como heteroátomo adicional; ii) un anillo heteroaromático de 5 a 10 miembros, monocíclico o bicíclico, que contiene uno o más átomos de nitrógeno que está opcionalmente sustituido con uno o más sustituyentes seleccionados de átomos de halógeno, alquilo C1-4, alcoxi C1-4, cicloalquilo C3-4, cicloalcoxi C3-4, -CF3, -OCF3, y -CONR7’R8’, en donde R7’ y R8’ se seleccionan independientemente a partir de átomo de hidrógeno, grupo alquilo C1-4 lineal o ramificado, grupo cicloalquilo C3-7, o R7’ y R8’ junto con el átomo de nitrógeno al que están unidos forman un grupo de fórmula (2) donde n es un número entero de 0 a 3; y iii) un grupo fenilo que está opcionalmente sustituido con uno o más sustituyentes seleccionados de átomos de halógeno, grupos alquilo C1-4, hidroxi, alcoxi C1-4, cicloalquilo C3-4, cicloalcoxi C3-4, ciano, -CF3, -OCF3, -CONR7’R8’, oxadiazolilo, triazolilo, pirazolilo e imidazolilo, en donde los grupos oxadiazolilo, triazolilo, pirazolilo e imidazolilo están opcionalmente sustituidos con un grupo alquilo C1-4 o un grupo cicloalquilo C3-7 y en donde R7’ y R8’ se seleccionan independientemente de un átomo de hidrógeno, un grupo alquilo C1-4 lineal o ramificado, un grupo cicloalquilo C3-7, o R7’ y R8’ junto con el átomo de nitrógeno al que están unidos forman un grupo de fórmula (2) donde n es un número entero de 0 a 3; o, cuando G1’ representa CR6’, G2’ junto con R6’ forman un grupo carbocíclico C5-10 no aromático o un grupo arilo C6-10.Compositions comprising specific amino derivatives for use in the treatment of proliferative diseases or disorders of the skin and the use of specific amino derivatives in said treatment are described. Claim 1: An amino derivative of formula (1): A-NH-B (1) or a pharmaceutically acceptable salt or N-oxide or solvate or deuterated derivative thereof, for use in the treatment of a disease or proliferative disorder of the skin, wherein: A represents a group of formula (A1) or (A2 ), where the asterisk symbol indicates the link that is attached to the rest -NH-B; and wherein: in the group of formula (A1): R1 represents a group selected from hydrogen atoms, halogen, C1-4 alkyl groups which may be optionally substituted with 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups , and C3-8 cycloalkyl groups which may be optionally substituted with 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups; one of the groups G3 and G4 is a nitrogen atom and the other is a CH group; M is a hydrogen atom or a pharmaceutically acceptable cation; in the group of formula (A2): R1 ’is selected from the group consisting of hydrogen atoms, halogen atoms, C1-4 alkyl, C3-4 cycloalkyl, -CF3 and -OCF3; R2 ’is selected from the group consisting of hydrogen atoms, halogen atoms and C1-4 alkyl group; R3 'is selected from the group consisting of the groups -COOR5', -CONHR5 ', tetrazolyl, -SO2NHR5' and -CONHSO2R5 ', where R5' is selected from the group consisting of a hydrogen atom and C1-4 alkyl groups linear or branched; B represents a group of formula (B1) or (B2), where the asterisk symbol indicates the link that is attached to the A-NH- moiety; and wherein: in the group of formula (B1): one of the groups G1 represents a nitrogen atom or a CRc group and the other represents a CRc group; G2 represents a nitrogen atom or a CRd group; R2 represents a group selected from hydrogen atoms, halogen atoms, hydroxyl groups, C1-4 alkyl groups which may be optionally substituted with 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, C1-4 alkoxy groups which may be optionally substituted with 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, and C3-8 cycloalkyl groups which may be optionally substituted with 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups; Ra, Rb, Rc independently represent groups selected from hydrogen atoms, halogen atoms, C1-4 alkyl groups which may be optionally substituted with 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, and C1-4 alkoxy groups which may be optionally substituted with 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups; Rd represents a group selected from hydrogen atoms, halogen atoms, hydroxyl groups, C1-4 alkyl groups which may be optionally substituted with 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, and C1-4 alkoxy groups which they may be optionally substituted with 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, and C3-8 cycloalkoxy groups which may be optionally substituted with 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups; with the proviso that, when at least one of the groups Ra and Rb represents a hydrogen atom and G2 is a CRd group, then Rd represents a group selected from C1-4 alkoxy groups that may be optionally substituted with 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, C3-8 cycloalkoxy groups which may be optionally substituted with 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups; in the group of formula (B2): R4 ’is selected from the group consisting of a hydrogen atom, and a C1-4 alkyl group; R9 ’is selected from the group consisting of a hydrogen atom and a phenyl group; G1 'represents a group selected from N and CR6' wherein R6 'is selected from the group consisting of hydrogen atoms, halogen atoms, C1-4 alkyl, C3-4 cycloalkyl, C1-4 alkoxy, -CF3, -OCF3 , C5-7 monocyclic heteroaryl containing N, C3-7 monocyclic heterocyclyl groups containing N and a C6-10 aryl group which is optionally substituted with one or more substituents selected from halogen atom and a C1-4 alkyl group; G2 'represents a group selected from: i) a hydrogen atom, a hydroxy group, a halogen atom, a C3-4 cycloalkyl group, a C1-4 alkoxy group and -NRa'Rb', where Ra 'represents a C1-4 alkyl group and Rb 'is selected from a group consisting of C1-4 alkyl group and C1-4 alkoxy group-C1-4 alkyl; or Ra 'and Rb' together with the nitrogen atom to which they are attached form a saturated 6 to 8 membered heterocyclic ring optionally containing an oxygen atom as an additional heteroatom; ii) a 5 to 10 membered heteroaromatic ring, monocyclic or bicyclic, containing one or more nitrogen atoms that is optionally substituted with one or more substituents selected from halogen atoms, C1-4 alkyl, C1-4 alkoxy, C3 cycloalkyl -4, C3-4 cycloalkoxy, -CF3, -OCF3, and -CONR7'R8 ', where R7' and R8 'are independently selected from hydrogen atom, linear or branched C1-4 alkyl group, C3 cycloalkyl group -7, or R7 'and R8' together with the nitrogen atom to which they are attached form a group of formula (2) where n is an integer from 0 to 3; and iii) a phenyl group that is optionally substituted with one or more substituents selected from halogen atoms, C1-4 alkyl groups, hydroxy, C1-4 alkoxy, C3-4 cycloalkyl, C3-4 cycloalkoxy, cyano, -CF3, - OCF3, -CONR7'R8 ', oxadiazolyl, triazolyl, pyrazolyl and imidazolyl, wherein the oxadiazolyl, triazolyl, pyrazolyl and imidazolyl groups are optionally substituted with a C1-4 alkyl group or a C3-7 cycloalkyl group and where R7' and R8 'are independently selected from a hydrogen atom, a linear or branched C1-4 alkyl group, a C3-7 cycloalkyl group, or R7' and R8 'together with the nitrogen atom to which they are attached form a group of formula ( 2) where n is an integer from 0 to 3; or, when G1 ’represents CR6’, G2 ’together with R6’ form a non-aromatic C5-10 carbocyclic group or a C6-10 aryl group.

ARP110103881A 2010-10-22 2011-10-20 AMINIC DERIVATIVES FOR THE TREATMENT OF SKIN PROLIFERATIVE DISORDERS AR083492A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP10382277A EP2444088A1 (en) 2010-10-22 2010-10-22 Amino derivatives for the treatment of proliferative skin disorders

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AR083492A1 true AR083492A1 (en) 2013-02-27

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EP (1) EP2444088A1 (en)
AR (1) AR083492A1 (en)
UY (1) UY33663A (en)
WO (1) WO2012052179A1 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10016402B2 (en) 2011-02-08 2018-07-10 Children's Medical Center Corporation Methods for treatment of melanoma
ES2788162T3 (en) * 2015-09-04 2020-10-20 Aslan Pharmaceuticals Pte Ltd Varlitinib for use in the treatment of resistant or refractory cancer
WO2018160138A1 (en) * 2017-03-02 2018-09-07 Aslan Pharmaceuticals Pte Ltd Dhodh inhibitor for treating haematological cancer
US11311548B2 (en) 2017-03-02 2022-04-26 Aslan Pharmaceuticals Pte. Ltd. Cancer therapy
CN108524482B (en) * 2017-03-02 2022-11-25 中国科学院上海药物研究所 Use of 2- (substituted phenylamino) benzoic acid FTO inhibitors for treating leukemia
GB201809102D0 (en) * 2018-06-04 2018-07-18 Univ Oxford Innovation Ltd Compounds

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003006424A1 (en) * 2001-07-10 2003-01-23 4Sc Ag Novel compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents
ES2319596B1 (en) 2006-12-22 2010-02-08 Laboratorios Almirall S.A. NEW DERIVATIVES OF THE AMINO-NICOTINIC AND AMINO-ISONICOTINIC ACIDS.
UY31272A1 (en) * 2007-08-10 2009-01-30 Almirall Lab NEW DERIVATIVES OF AZABIFENILAMINOBENZOIC ACID
EP2228367A1 (en) * 2009-03-13 2010-09-15 Almirall, S.A. Addition salts of amines containing hydroxyl and/or carboxylic groups with amino nicotinic acid derivatives as DHODH inhibitors
EP2239256A1 (en) * 2009-03-13 2010-10-13 Almirall, S.A. Sodium salt of 5-cyclopropyl-2-{[2-(2,6-difluorophenyl)pyrimidin-5-yl]amino}benzoic acid as DHODH inhibitor

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EP2444088A1 (en) 2012-04-25
WO2012052179A1 (en) 2012-04-26
UY33663A (en) 2012-05-31

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